Blood vessel model

ABSTRACT

A blood vessel model which imitates a human blood vessel including an aqueous gel made from polyvinyl alcohol having an average polymerization degree of 300 to 3500 and a saponification degree of 90% by mole or more, and silica particles; and a method for producing a blood vessel model which imitates a human blood vessel, including filling a mixed solution containing polyvinyl alcohol having an average polymerization degree of 300 to 3500 and a saponification degree of 90% by mole or more, silica particles and water in a mold for forming a blood vessel model, and freezing the mixture at a temperature of −10° C. or lower, followed by thawing. The blood vessel model can be suitably used as a blood vessel model for practicing insertion of a stent graft into an aneurysm, a blood vessel model for practicing resection or ligation surgery of a blood vessel, and the like.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Divisional application of U.S. application Ser.No. 13/392,177, filed Feb. 24, 2012, and wherein application Ser. No.13/392,177 is a national stage application filed under 35 USC §371 ofInternational Application No. PCT/JP2010/065473, filed Sep. 9, 2010, andwhich is based upon and claims the benefit of priority from the priorJapanese Patent Application Nos. 2009-228296, 2009-228305 and2009-131590, filed on Sep. 30, 2009, Sep. 30, 2009, and May 29, 2009,respectively, the entire contents of which are incorporated herein byreference.

TECHNICAL FIELD

The present invention relates to a blood vessel model. Moreparticularly, the present invention relates to a blood vessel modelwhich imitates a human blood vessel, and which can be suitably used, forexample, as a blood vessel model for practicing insertion of a stentgraft into an aneurysm, a blood vessel model for practicing resection orligation surgery of a blood vessel, and the like.

BACKGROUND ART

Among surgeries carried out by surgeons, insertion of a stent graft intoan aneurysm and resection or ligation surgery of a blood vessel requirecareful and skilled techniques, which spell the difference between lifeand death. Therefore, it is necessary for medical interns and medicalstudents as well as vascular surgeons to repeatedly carry out surgicaltraining by using a blood vessel model so as to learn skilledtechniques.

There have hitherto been proposed, as a material which constitutes ablood vessel model for practicing surgery, a synthetic rubber, adiene-based rubber, and the like (see, for example, paragraph [0009] inPatent Literature 1 and paragraph [0015] in Patent Literature 2); anatural rubber, a silicone rubber, an acrylic rubber, an olefinicrubber, polyurethane, and the like (see, for example, paragraph [0006]in Patent Literature 3, paragraph [0006] in Patent Literature 4,paragraph [0015] in Patent Literature 5 and paragraph [0013] in PatentLiterature 6); polyvinyl chloride, polybutadiene, ionomer, low densitypolyethylene, and the like (see, for example, paragraph [0017] in PatentLiterature 7); and the like. A tube made of a silicone rubber has beenwidely used among these materials, since the silicone rubber iscomparatively similar to a blood vessel of the human body. However,since the above-mentioned materials such as the silicone rubber havevery strong water repellency, the materials have neither hydrophilicitynor flexibility like the blood vessel of the human body. Therefore, itcannot be said that the blood vessel model made of the material issuited for vascular surgeons to perform manipulation training.

Accordingly, it has recently been required by researchers of medicalcolleges, surgical hospitals and the like, including vascular surgeons,to develop a blood vessel model which can be suitably used as a bloodvessel model for practicing resection or ligation surgery of a bloodvessel, a blood vessel model for practicing insertion of a stent graftinto an aneurysm, and the like.

PRIOR ART DOCUMENTS Patent Literatures

-   Patent Literature 1: Japanese utility model publication No. Hei    05-0027776-   Patent Literature 2: Japanese patent publication No. 2005-195696-   Patent Literature 3: Japanese utility model publication No. Hei    06-0004768-   Patent Literature 4: Japanese patent publication No. Hei 11-0167342-   Patent Literature 5: Japanese patent publication No. 2007-316343-   Patent Literature 6: Japanese patent publication No. 2008-261990-   Patent Literature 7: Japanese patent publication No. 2006-126686

SUMMARY OF THE INVENTION Problems to be Solved by the Invention

An object of the present invention is to provide a blood vessel modelwhich has moderate hydrophilicity, flexibility (resilience) and asurface free from stickiness, and which can be suitably used as a bloodvessel model for practicing insertion of a stent graft into an aneurysm,a blood vessel model for practicing resection or ligation surgery of ablood vessel, and the like.

Means for Solving the Problems

The present invention relates to

(1) a blood vessel model which imitates a human blood vessel, includingan aqueous gel made from polyvinyl alcohol having an averagepolymerization degree of 300 to 3500 and a saponification degree of 90%by mole or more, and silica particles;(2) the blood vessel model according to the above (1), wherein colloidalsilica is used as the silica particles;(3) the blood vessel model according to the above (1) or (2), whereinthe amount of the silica particles is from 0.01 to 50 parts by weightbased on 100 parts by weight of the polyvinyl alcohol;(4) the blood vessel model according to any one of the above (1) to (3),wherein the blood vessel model is produced by freezing a mixed solutioncontaining the polyvinyl alcohol, the silica particles and water at atemperature of −10° C. or lower, followed by thawing;(5) the blood vessel model according to the above (1), wherein theaqueous gel is a cross-linked gel;(6) the blood vessel model according to the above (5), wherein thecross-linked gel is a cross-linked gel being cross-linked with dimethylsulfoxide;(7) the blood vessel model according to the above (6), wherein the bloodvessel model is produced by cooling a mixed solution containingpolyvinyl alcohol, silica particles, dimethyl sulfoxide and water to atemperature of −10° C. or lower, followed by thawing;(8) a method for producing a blood vessel model which imitates a humanblood vessel, which includes filling a mixed solution containingpolyvinyl alcohol having an average polymerization degree of 300 to 3500and a saponification degree of 90% by mole or more, silica particles andwater in a mold for forming a blood vessel model, and freezing themixture at a temperature of −10° C. or lower, followed by thawing;(9) the method for producing a blood vessel model according to the above(8), wherein colloidal silica is used as the silica particles;(10) the method for producing a blood vessel model according to theabove (8) or (9), wherein the amount of the silica particles is from0.01 to 50 parts by weight based on 100 parts by weight of the polyvinylalcohol;(11) the method for producing a blood vessel model according to any oneof the above (8) to (10), wherein the concentration of the polyvinylalcohol in the mixed solution is from 1 to 40% by weight;(12) the method for producing a blood vessel model according to any oneof the above (8) to (11), wherein the temperature of the blood vesselmodel formed after thawing is controlled to 35° to 80° C.;(13) the method for producing a blood vessel model according to any oneof the above (8) to (12), wherein the mixed solution further containsdimethyl sulfoxide; and(14) the method for producing a blood vessel model according to theabove (13), wherein the ratio of the dimethyl sulfoxide to water(dimethyl sulfoxide/water: volume ratio) is from 50/50 to 95/5.

Effects of the Invention

The blood vessel model of the present invention has moderatehydrophilicity and flexibility (resilience), and has a surface free fromstickiness. Therefore, the blood vessel model can be suitably used as ablood vessel model for practicing insertion of a stent graft into ananeurysm, a blood vessel model for practicing resection or ligationsurgery of a blood vessel, and the like.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 A photograph, which is substituted for a drawing, of a bloodvessel model obtained in Example 1 of the present invention.

FIGS. 2 a, b, c Schematic drawings for the explanation of manipulationtraining carried out by inserting a stent graft into the blood vesselmodel having a large aneurysm of the present invention.

FIG. 3 A photograph, which is substituted for a drawing, of a bloodvessel model obtained in Example 6 of the present invention.

FIG. 4 A photograph, which is substituted for a drawing, of a bloodvessel model obtained in Example 7 of the present invention.

FIG. 5 A photograph, which is substituted for a drawing, of a bloodvessel model obtained in Example 14 of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The blood vessel model of the present invention is a blood vessel modelwhich imitates a human blood vessel. The blood vessel model ischaracterized in that the blood vessel model contains an aqueous gelmade from polyvinyl alcohol having an average polymerization degree of300 to 3500 and a saponification degree of 90% by mole or more, andsilica particles.

The blood vessel model of the present invention can be easily produced,for example, by freezing a mixed solution containing polyvinyl alcoholhaving an average polymerization degree of 300 to 3500 and asaponification degree of 90% by mole or more, water and silica particlesat a temperature of −10° C. or lower, followed by thawing.

The average polymerization degree of the polyvinyl alcohol as determinedby a viscosity method is preferably 300 or more, more preferably 500 ormore, and still more preferably 1000 or more from the viewpoint ofincrease in mechanical strength such as tensile strength of the bloodvessel model of the present invention, and preferably 3500 or less, morepreferably 3000 or less, and still more preferably 2500 or less from theviewpoint of imparting of moderate flexibility (resilience).

The saponification degree of the polyvinyl alcohol is preferably 90% bymole or more, more preferably 95% by mole or more, and still morepreferably 98% by mole or more from the viewpoint of increase inmechanical strength such as tensile strength and flexibility(resilience) of the blood vessel model of the present invention. Thereis no limitation in the upper limit of the saponification degree of thepolyvinyl alcohol. It is preferred that the higher the saponificationdegree of the polyvinyl alcohol is, and it is more preferable that thepolyvinyl alcohol is a completely saponified polyvinyl alcohol.

The polyvinyl alcohol can be usually used in the form of an aqueoussolution. When the polyvinyl alcohol is dissolved in water, thepolyvinyl alcohol or water is preferably warmed in advance from theviewpoint of increase in solubility of the polyvinyl alcohol. Theconcentration of the polyvinyl alcohol in the aqueous solution of thepolyvinyl alcohol is preferably 1% by weight or more, more preferably 3%by weight or more, and still more preferably 5% by weight or more fromthe viewpoint of increase in mechanical strength of the blood vesselmodel of the present invention, and the concentration of the polyvinylalcohol is preferably 40% by weight or less, more preferably 30% byweight or less, and still more preferably 20% by weight or less from theviewpoint of improvement in moldability as well as sufficientdissolution of the ving polyvinyl alcohol in water.

The blood vessel model of the present invention has one of greatfeatures in that the blood vessel model contains silica particles. Sincethe blood vessel model of the present invention contains silicaparticles, the blood vessel model has a surface free from stickiness,and also has moderate hydrophilicity and flexibility (resilience).Therefore, the blood vessel model of the present invention can besuitably used as a blood vessel model for practicing insertion of astent graft into an aneurysm, a blood vessel model for practicingresection or ligation surgery of a blood vessel, and the like.

In the present invention, the silica particles and the polyvinyl alcoholare used in combination as raw materials. Therefore, it is possible toefficiently obtain a blood vessel model which has a surface free fromstickiness, also has moderate hydrophilicity and flexibility(resilience), and is excellent in mechanical strength such as tensilestrength, by performing freezing and thawing of a mixed solutioncontaining the silica particles and the polyvinyl alcohol only oncewithout the repetition of an operation of freezing and thawing of thepolyvinyl alcohol solution plural times, like in a conventional method.

The particle diameter of the silica particles is preferably from 3 to100 nm or so from the viewpoint of enhancement in dispersion stabilityof the silica particles in the polyvinyl alcohol and smoothness of theblood vessel model of the present invention.

The amount of the silica particles is preferably 0.01 parts by weight ormore, more preferably 0.05 parts by weight or more, and still morepreferably 0.1 parts by weight or more based on 100 parts by weight ofthe polyvinyl alcohol from the viewpoint of increase in mechanicalstrength and flexibility (resilience) of the blood vessel model of thepresent invention, and preferably 50 parts by weight or less, morepreferably 30 parts by weight or less, and still more preferably 20parts by weight or less from the viewpoint of preventing the bloodvessel model of the present invention from becoming hard. The silicaparticles can be usually mixed with the polyvinyl alcohol or its aqueoussolution.

In the present invention, it is preferred that the silica particles areused in the form of colloidal silica. When the colloidal silica is usedas the silica particles, it is possible to obtain a blood vessel modelwhich has a surface free from stickiness and has moderate hydrophilicityand flexibility (resilience), and which can be suitably used as a bloodvessel model for practicing insertion of a stent graft into an aneurysm,a blood vessel model for practicing resection or ligation surgery of ablood vessel, and the like.

The content of the silica particles in the colloidal silica ispreferably from 3 to 40% by weight or so from the viewpoint ofimprovement in dispersion stability of the silica particles in thecolloidal silica. The colloidal silica is commercially available, forexample, from Nissan Chemical Industries, Ltd. under the trade name ofSNOWTEX (registered trademark), and the like.

It is preferred that the aqueous gel is a cross-linked gel from theviewpoint of obtaining a blood vessel model of the present invention,which has moderate hydrophilicity, flexibility (resilience) and asurface free from stickiness, and which also has a large tensilestrength.

It is preferred that the cross-linked gel is a cross-linked gel beingcross-linked with dimethyl sulfoxide from the viewpoint of producing ablood vessel model having moderate hydrophilicity, flexibility(resilience) and a surface free from stickiness, and also having a largetensile strength.

The blood vessel model containing the cross-linked gel and the silicaparticles of the present invention can be easily produced, for example,by cooling a mixed solution containing polyvinyl alcohol having anaverage polymerization degree of 300 to 3500 and a saponification degreeof 90% by mole or more, silica particles, dimethyl sulfoxide and waterto a temperature of −10° C. or lower, followed by thawing.

The polyvinyl alcohol can be added to a mixed solvent of dimethylsulfoxide and water, water used in the mixed solvent, or a mixtureprepared by adding the silica particles to the mixed solvent. It ispreferred that the mixed solvent, water to be used in the mixed solvent,or the mixed solution is heated prior to the addition of the polyvinylalcohol from the viewpoint of increase in solubility of the polyvinylalcohol. There is no particular limitation in heating temperature incase of heating, and usually, it is preferred that the heatingtemperature is from 60° to 95° C. or so.

In the blood vessel model containing the cross-linked gel and the silicaparticles of the present invention, the content of the polyvinyl alcoholin the mixed solution containing the polyvinyl alcohol, the silicaparticles, dimethyl sulfoxide and water is preferably 1% by weight ormore, more preferably 3% by weight or more, and still more preferably 5%by weight or more from the viewpoint of increase in mechanical strengthsuch as tensile strength of the blood vessel model of the presentinvention, and the content of the polyvinyl alcohol is preferably 40% byweight or less, more preferably 30% by weight or less, and still morepreferably 20% by weight or less from the viewpoint of increase insolubility of the polyvinyl alcohol and prevention of stickiness.

The ratio of dimethyl sulfoxide to water (dimethyl sulfoxide/water:volume ratio) is preferably 50/50 or more, more preferably 60/40 ormore, and still more preferably 70/30 or more from the viewpoint ofincrease in mechanical strength such as tensile strength of the bloodvessel model of the present invention, and the ratio is preferably 95/5or less, more preferably 90/10 or less, and still more preferably 85/15or less from the viewpoint of suppression of stickiness of the surface,and enhancement of flexibility (resilience) and hydrophilicity of theblood vessel model of the present invention.

In the blood vessel model containing the cross-linked gel and the silicaparticles of the present invention, the amount of the silica particlesis preferably 0.01 parts by weight or more, more preferably 0.05 partsby weight or more, and still more preferably 0.1 parts by weight or morebased on 100 parts by weight of water from the viewpoint of increase inmechanical strength such as tensile strength, prevention of stickinessand imparting moderate hydrophilicity of the blood vessel model of thepresent invention, and the amount of the silica particles is preferably50 parts by weight or less, more preferably 30 parts by weight or less,and still more preferably 20 parts by weight or less from the viewpointof enhancement in flexibility (resilience) of the blood vessel model ofthe present invention. When the silica particles are used in the form ofcolloidal silica, the amount of the above-mentioned water includes theamount of the water contained in the colloidal silica.

In the blood vessel model containing the cross-linked gel and the silicaparticles of the present invention, a mixed solution containing thepolyvinyl alcohol, the silica particles, dimethyl sulfoxide and water iscooled to a desired temperature for a desired period of time to frozenthe mixed solution. When the mixed solution is frozen, the mixedsolution is gelled by cross-linking, and thereby a molded productcontaining a cross-linked gel and the silica particles is formed.

It is preferred that polysaccharide is added to the polyvinyl alcoholfrom the viewpoint of preventing the surface layer of a molded productfrom drying. It is preferred that the polysaccharide is added to themixed solution from the viewpoint of increase in dispersion stability.

The polysaccharide includes, for example, chitin, deacetylated chitin,chitosan, chitosan acetate, chitosan maleate, chitosan glyconate,chitosan sorbate, chitosan formate, chitosan salicylate, chitosanpropionate, chitosan lactate, chitosan itaconate, chitosan niacinate,chitosan gallate, chitosan glutamate, carboxymethyl chitosan, alkylcellulose, nitrocellulose, hydroxypropyl cellulose, starch, collagen,alginate, hyaluronic acid, heparin, and the like. However, the presentinvention is not limited only to those exemplified ones. Among thesepolysaccharides, chitosan and its derivative are preferable, andchitosan is more preferable from the viewpoint of preventing the bloodvessel model of the present invention from drying.

The chitosan includes, for example, those obtained by deacetylatingchitin derived from crustaceans such as prawn, crab and cuttlefish. Thechitosan is commercially easily available. The chitosan can be usuallyused in the form of powder. The molecular weight of the chitosan is notparticularly limited, and is usually preferably from 10000 to 200000,and more preferably from 10000 to 40000.

The amount of the polysaccharide cannot be absolutely determined becausethe amount varies depending on its kind, and the amount is usuallypreferably 0.3 parts by weight or more, more preferably 0.5 parts byweight or more, and still more preferably 1 part by weight or more basedon 100 parts by weight of the polyvinyl alcohol from the viewpoint ofpreventing the blood vessel model of the present invention from drying,and the amount is preferably 300 parts by weight or less, morepreferably 250 parts by weight or less, and still more preferably 200parts by weight or less from the viewpoint of imparting moderateresilience to the blood vessel model of the present invention.

It is preferred that polysaccharide is usually used in the form ofaqueous solution from the viewpoint of enhancement in dispersionstability. The aqueous solution of the polysaccharide can be obtained,for example, by dissolving the polysaccharide in an aqueous solution ofan acid such as acetic acid, hydrochloric acid or lactic acid so as tohave a concentration of 0.5 to 10% by weight or so. The aqueous solutionof the polysaccharide can be controlled to neutral to basic with a basicsubstance such as sodium hydroxide or potassium hydroxide as occasiondemands.

The mixed solution may contain an additive, for example, a colorant suchas a pigment or a dye, a perfume, an antioxidant, a mildewproofing agentor an antibacterial agent in a proper amount, so long as an object ofthe present invention is not hindered. It is preferred that theseadditives are usually added to the mixed solution from the viewpoint ofimprovement in dispersion stability. In order to make the blood vesselmodel of the present invention similar to a blood vessel of the humanbody, it is preferred to tint the mixed solution to the color similar toa blood vessel of the human body with a colorant.

The blood vessel model of the present invention can be produced byfilling a mixed solution containing the polyvinyl alcohol, water, thesilica particles and dimethyl sulfoxide as occasion demands into a moldfor forming a blood vessel model, and freezing the mixed solution at atemperature of −10° C. or lower, followed by thawing.

More specifically, the blood vessel model of the present invention canbe produced, for example, by filling the mixed solution into a tubehaving an inner diameter corresponding to the diameter of a blood vesselof the human body; freezing the mixed solution at a temperature of −10°C. or lower; thawing the frozen mixed solution; inserting a striped bodyhaving a diameter corresponding to the inner diameter of the bloodvessel, such as a galvanized steel wire, a wire or a metal wire into thecentral portion of a molded product formed in the tube to form a passageof blood; and removing the tube and the striped body from the moldedproduct. When the striped body is inserted into the central portion ofthe molded product, the molded product may be taken out from theinterior of the tube through suction or extruding, followed by insertionof a striped body into the central portion of the molded product to forma passage of blood.

The tube includes, for example, a rubber tube made of a silicone rubber,a tube made of an elastomer, a resin tube made of a resin such aspolypropylene, an acrylic resin or polycarbonate, and the like. However,the present invention is not limited only to those exemplified ones.

In the present invention, the blood vessel model can be produced, forexample, by filling a mixed solution into a straight tube having aninner diameter corresponding to the external form of a blood vessel;inserting a core material having a diameter corresponding to the innerdiameter of the blood vessel into the central portion of the straighttube; freezing the mixed solution at a temperature of −10° C. or lower;thawing the frozen mixed solution; and removing the straight tube andthe core material from the molded product.

The straight tube includes, for example, a resin tube made of asynthetic resin such as polypropylene, hard polyethylene, hard polyvinylchloride, an acrylic resin, a polyester or polycarbonate, a glass tube,and the like. However, the present invention is not limited only tothose exemplified ones. It is preferred that the inner diameter of thestraight tube is determined in accordance with the diameter of a bloodvessel of the living body.

The core material to be inserted into the straight tube includes, forexample, a core material made of a synthetic resin such aspolypropylene, hard polyethylene, hard vinyl chloride, an acrylic resin,a polyester or polycarbonate, a core material made of glass, a corematerial made of a metal, and the like. However, the present inventionis not limited only to those exemplified ones.

In order to allow the core material inserted into the straight tube tobe located at the central portion of the straight tube, it is preferred,for example, that an opening at one end of the straight tube is sealedwith a shield plug having a through hole for inserting a core materialinto the central portion of the straight tube, and the core material isinserted into the through hole. In this case, the opening at one end ofthe straight tube may be sealed with the shield plug after inserting thecore material into the through hole of the shield plug. The shield plugincludes, for example, a rubber plug made of a rubber such as siliconerubber or natural rubber, a cork plug, and the like. However, thepresent invention is not limited only to those exemplified ones.

In the straight tube of which opening at one end is sealed with theshield plug and into which the core material is inserted, it ispreferred that a mixed solution is poured in the gap between thestraight tube and the core material, and then an opening at another endof the straight tube is sealed with a shield plug having a through holefor inserting the core material into the central portion in the samemanner as described above. Next, the core material is inserted into thestraight tube at the central portion. The mixed solution is poured tothe inside of the strait tube, and thereafter the straight tube issealed with a shield plug at both ends. The straight tube is frozen at atemperature of −10° C. or lower so as to gel the mixed solution.

The freezing temperature of the mixed solution is preferably −10° C. orlower, more preferably −15° C. or lower, and still more preferably −20°C. or lower from the viewpoint of increase in mechanical strength of theblood vessel model of the present invention, and the freezingtemperature is preferably −35° C. or higher, and more preferably −30° C.or higher from the viewpoint of enhancement in productive efficiency ofthe blood vessel model of the present invention.

The period of time for cooling the mixed solution to the above-mentionedtemperature is preferably from 1 to 10 hours or so, and more preferablyfrom 3 to 8 hours or so from the viewpoint of increase in mechanicalstrength of the blood vessel model of the present invention andenhancement in productive efficiency.

The mixed solution is frozen by cooling to a desired temperature for adesired period of time. In this case, since the mixed solution isgelled, a molded product containing the aqueous gel and the silicaparticles is formed.

Next, the molded product is thawed. The molded product may be naturallythawed, for example, by allowing the molded product to stand at roomtemperature, or may be thawed by heating. From the viewpoint of increasein energy efficiency, natural thawing is preferable. The temperature atwhich the molded product is thawed is not particularly limited, and canbe usually from room temperature to 40° C. or so, and preferably from10° to 40° C. or so.

The blood vessel model of the present invention can be obtained bythawing the molded product in the above manner. The obtained bloodvessel model can be used as it is without drying. The blood vessel modelmay be dried as occasion demands so as to make the blood vessel modelsimilar to the blood vessel of the living body. The degree of dryingcannot be absolutely determined since the degree varies depending on thekind of the blood vessel of the living body. Therefore, it is preferredthat the degree of drying is appropriately controlled in accordance withthe kind of the blood vessel. When the blood vessel model is dried byheating, the texture of the aqueous gel constituting the blood vesselmodel can be homogenized.

For example, when the blood vessel model is dried by heating, the bloodvessel model can be dried in a drying chamber. When the blood vesselmodel is dried, the temperature of the blood vessel model is preferably35° C. or higher, and more preferably 40° C. or higher from theviewpoint of homogenizing the texture of the aqueous gel, and thetemperature is preferably 80° C. or lower, and more preferably 75° C. orlower from the viewpoint of improvement in gel elasticity andflexibility (resilience) of the blood vessel model. The period of timenecessary for controlling the temperature of the blood vessel model tothe above temperature cannot be absolutely determined, because theperiod of time varies depending on the temperature. It is preferred thatthe period of time is usually from 0.5 to 3 hours or so from theviewpoint of homogenizing the texture of the aqueous gel constitutingthe blood vessel model. After the temperature of the blood vessel modelis controlled, the blood vessel model may be allowed to stand to cool toroom temperature.

The blood vessel model of the present invention is usually produced soas to have an outer diameter and an inner diameter similar to those ofthe blood vessel of the human body. Therefore, it is preferred that theouter diameter of the blood vessel model of the present invention isusually controlled to 2 to 5 mm or so, and that the inner diameter ofthe blood vessel model is usually controlled to 1 to 3 mm or so.

The blood vessel model of the present invention can be used as a bloodvessel model as it is, and may be cut so as to have a desired length asoccasion demands. The blood vessel model of the present invention alsocan be produced by molding a blood vessel model having a predeterminedouter diameter and a predetermined inner diameter which are larger thanthose of a blood vessel of the human body, and drawing the blood vesselmodel to have a desired outer diameter and a desired inner diameter.

The internal of the blood vessel model of the present invention may behollow. Alternatively, the internal can be filled with a liquid similarto blood. For example, when the internal of the blood vessel model isfillee with a liquid having a color similar to that of blood, the bloodvessel model can be used as a blood vessel model filled with the liquidsimilar to the blood.

In the blood vessel model of the present invention, an aneurysm-shapedblood vessel model which imitates an aneurysm having a diameter ofseveral cm, for example, 3 to 6 cm or so may be formed between one bloodvessel model and another blood vessel model.

The aneurysm-shaped blood vessel model can be produced, for example, byapplying the above-mentioned mixed solution to the surface of aballoon-shaped spherical body having a predetermined diameter, which isexpanded by blowing air into the spherical body, followed by freezingand thawing in accordance with the method for producing a blood vesselmodel of the present invention. The spherical body in theaneurysm-shaped blood vessel model can be removed by shrinkage. When theshrunk spherical body is removed from the aneurysm-shaped blood vesselmodel, a hole can be formed in this blood vessel model. This hole can beused as a passage of blood by connecting this hole with the inner holeof a straight tubular blood vessel model.

The blood vessel model in which an aneurysm-shaped blood vessel model isconnected with a straight tubular blood vessel model can be produced,for example, by bonding the aneurysm-shaped blood vessel model with thestraight tubular blood vessel model to connect the inside space of bothmodels with each other, and applying a mixed solution to the connectedportion of both models, followed by freezing and thawing in accordancewith the method for producing a blood vessel model of the presentinvention. When a blood vessel model is produced in the above manner,the leakage of a liquid being filled in the blood vessel can be avoidedat the connected portion of the aneurysm-shaped blood vessel model andthe straight tubular blood vessel model.

The aneurysm-shaped blood vessel model thus obtained can be suitablyused, for example, as a blood vessel model for practicing insertion of astent graft into a large aneurysm, a blood vessel model for practicingsurgery including resecting a large aneurysm, and then implanting anartificial blood vessel in place of the large aneurysm, and the like.Its one embodiment is described below with reference to a drawing.

FIG. 2 is a schematic drawing for the explanation of manipulationtraining carried out by inserting a stent graft into the blood vesselmodel having a large aneurysm of the present invention.

FIG. 2( a) shows a blood vessel model having a large aneurysm 2 formedin an aorta 1. When the large aneurysm 2 existing in the human body isallowed to stand as it is, the large aneurysm 2 may rupture, resultingin death. Therefore, as shown in FIG. 2( b), a catheter 4 including astent graft 3 is inserted to the position where the large aneurysm 2exists, and the stent graft 3 is taken out from the catheter 4 at theposition where the large aneurysm 2 exists. Thereafter, the stent graft3 is spread in the aorta 1 so as to cover the large aneurysm 2. Sincethe large aneurysm 2 is covered with the stent graft 3 by the aboveoperation, blood does not flow into the large aneurysm 2. Therefore, asshown in FIG. 2( c), the large aneurysm 2 shrinks, and thus rupture ofthe large aneurysm 2 can be prevented.

The practice of treatment of the large aneurysm by using such a stentgraft cannot be applied to the living body. Therefore, it has recentlybeen desired to develop a blood vessel model for practicing insertion ofa stent graft into the aorta. This desire can be satisfied with theblood vessel model of the present invention.

The blood vessel model of the present invention can be used as a bloodvessel model for practicing resection of a blood vessel portion having alarge aneurysm and implantation of an artificial blood vessel in placeof the resected blood vessel portion. In this case, it is possible touse a blood vessel model having a large aneurysm 2 in an aorta 1 asshown in FIG. 2( a). In this case, for example, bleeding is stopped byclipping the blood vessel before and after the large aneurysm 2 of ablood vessel model with forceps. After resecting the blood vessel modelhaving the large aneurysm 2 between both forceps, a blood vessel modelhaving a healthy blood vessel shape is applied to the thus resectedposition, followed by ligation of both end portions of this blood vesselmodel with the blood vessel model in which the large aneurysm 2 isresected. Thus, treatment practice is completed.

Accordingly, it is possible to practice resecting a blood vessel havingan aneurysm in an aorta and practice ligating both end portions of thethus resected blood vessel and a healthy blood vessel by using the bloodvessel model of the present invention as a blood vessel model forpracticing manipulation in which a blood vessel portion having a largeaneurysm is resected and an artificial blood vessel is implanted inplace of the resected blood vessel portion.

In the present invention, as described above, the silica particles andthe polyvinyl alcohol are used in combination as raw materials.Therefore, it is possible to efficiently obtain a blood vessel modelwhich has hydrophilicity like a blood vessel of the human body and asurface free from stickiness, and which also has flexibility(resilience), incision feeling like a blood vessel of the human body andsatisfactory mechanical strength, by performing freezing and thawing ofthe mixed solution only one time without the repeating of an operationfor freezing and thawing of the mixed solution plural times.Incidentally, the operation for freezing and thawing may be repeatedplural times as occasion demands.

As described above, the blood vessel model of the present invention hashydrophilicity like a blood vessel of the human body and a surface freefrom stickiness, and also has flexibility (resilience) and incisionfeeling like a blood vessel of the human body. Also, the blood vesselmodel containing the cross-linked gel and the silica particles of thepresent invention has a surface free from stickiness, and also hasmoderate hydrophilicity, flexibility (resilience) and a suitable tensilestrength.

Accordingly, the blood vessel model of the present invention can besuitably used, for example, as a blood vessel model for practicinginsertion of a stent graft into a blood vessel having an aneurysm, and ablood vessel model for practicing resection or ligation surgery of ablood vessel.

EXAMPLES

Next, the present invention will be more specifically described by wayof examples, but the present invention is not limited only to thoseexamples.

Example 1

A polyvinyl alcohol having an average polymerization degree of 1700 anda saponification degree of about 98 to about 99% by mole [manufacturedby KURARAY CO., LTD. under the trade name of KURARAY POVAL PVA-117] wasdissolved in water to prepare an aqueous polyvinyl alcohol solution inwhich the concentration of polyvinyl alcohol was 10% by weight. Afterstirring the obtained aqueous polyvinyl alcohol solution for 15 minuteswhile warming to 80° C., the solution was allowed to stand to cool toroom temperature. This aqueous polyvinyl alcohol solution in an amountof 500 mL was charged in a 1 L (liter) beaker.

Next, 15 mL of colloidal silica [manufactured by Nissan ChemicalIndustries, Ltd. under the trade name of SNOWTEX XP, particle diameterof silica: about 5 nm, content of silica: 5% by weight] was added to thebeaker at room temperature, followed by stirring so as to form uniformcontents in the beaker, to give a mixed solution.

To the mixed solution in the beaker, 0.5 mL of a semitransparent acrylicposter color having a chestnut color similar to the color of a humanblood vessel [manufactured by Delta Corporation under the trade name ofDeltaCeramcoat] was added, followed by stirring so as to form uniformcomponents.

A rubber plug made of a silicone rubber was inserted into the opening atone end of a straight tube made of an acrylic resin and having a outerdiameter of 5 mm, an inner diameter of 4 mm and a length of 200 mm, anda core material made of an acrylic resin having a diameter of 2 mm and alength of 250 mm was inserted into the hole for inserting a corematerial provided at the central portion of the rubber plug. The openingat another end of this straight tube was faced upward, and the tintedmixed solution obtained in the above (liquid temperature: 20° C.) waspoured into the gap between the straight tube and the core material upto the vicinity of the opening at another end of the straight tube sothat no air bubbles infiltrated. Thereafter, a core material waspenetrated into the hole for inserting the core material provided at thecentral portion of the rubber plug made of a silicone rubber, and therubber plug was inserted into the opening of the straight tube.

Next, this straight tube was placed in a freezing chamber (temperaturein the freezing chamber: −20° C.), cooled for 5 hours, taken out fromthe freezing chamber and then allowed to stand at room temperature tohave room temperature.

Next, this straight tube was placed in a dryer, heated to 60° C.,maintained at the same temperature for 10 minutes, taken out from thedryer, and then allowed to stand to cool.

The obtained blood vessel model was taken out from this straight tube.The core material was taken out from this blood vessel model, and thendried to give a blood vessel model similar to a blood vessel of thehuman body. An acrylic poster color having a red color similar to thecolor of human blood [manufactured by Delta Corporation under the tradename of DeltaCeramcoat] was filled into the obtained blood vessel model.The blood vessel model thus obtained is shown in FIG. 1. FIG. 1 is aphotograph, which is substituted for a drawing, of the blood vesselmodel. As shown in FIG. 1, a liquid similar to blood (black area in thedrawing) exists inside the obtained blood vessel model, and it can beseen that the blood vessel model has a form similar to a blood vessel ofthe human body.

Example 2

A blood vessel model was produced in the same manner as in Example 1,except that polyvinyl alcohol having an average polymerization degree of1000 and a saponification degree of about 98 to about 99% by mole[manufactured by KURARAY CO., LTD. under the trade name of KURARAY POVALPVA-110] was used as polyvinyl alcohol in Example 1.

Example 3

A blood vessel model was produced in the same manner as in Example 1,except that polyvinyl alcohol having an average polymerization degree of2000 and a saponification degree of about 98 to about 99% by mole[manufactured by KURARAY CO., LTD. under the trade name of KURARAY POVALPVA-120] was used as polyvinyl alcohol in Example 1.

Example 4

A blood vessel model was produced in the same manner as in Example 1,except that the amount of colloidal silica was changed to 1 mL inExample 1.

Example 5

A blood vessel model was produced in the same manner as in Example 1,except that the amount of the colloidal silica was changed to 80 mL inExample 1.

Comparative Example 1

A blood vessel model was produced in the same manner as in Example 1,except that the colloidal silica was not used in Example 1.

Comparative Example 2

A polyvinyl alcohol powder (average polymerization degree: 1700,saponification degree: 99.0% by mole) in an amount of 80 g was mixedwith a polyvinyl alcohol powder (average polymerization degree: 1800,saponification degree: 86 to 90% by mole) in an amount of 20 g to obtaina polyvinyl alcohol mixture. The obtained polyvinyl alcohol mixture wasdissolved in a mixed solvent of dimethyl sulfoxide and water [dimethylsulfoxide/water (weight ratio): 80/20] while heating to 120° C. toprepare a polyvinyl alcohol solution having a water content of 80% byweight.

The same procedures as in Example 1 were carried out except that thepolyvinyl alcohol solution obtained in the above was used in place ofthe mixed solution used in Example 1. The polyvinyl alcohol solutionobtained in the above (liquid temperature: 45° C.) was poured into thegap between the straight tube and the core material up to the vicinityof the opening at another end of the straight tube so that no airbubbles infiltrated. Then, a core material was penetrated into the holefor inserting a core material provided at the central portion of arubber plug made of a silicone rubber, and the rubber plug was insertedinto the opening of the straight tube.

Next, this straight tube was placed in a freezing chamber (temperaturein the freezing chamber: −20° C.), cooled for 6 hours, taken out fromthe freezing chamber, and then allowed to stand at room temperature, tohave room temperature. The rubber plug at both ends of this straighttube was removed, and the core material was taken out from the straighttube. This straight tube was dipped in 200 mL of ethanol for 2 hours atroom temperature, whereby dimethyl sulfoxide was substituted withethanol to remove. After dipping the straight tube in water at 25° C.,this straight tube was taken out from the water, and the obtained bloodvessel model was taken out from the straight tube.

This blood vessel model was observed with naked eyes. As a result, itwas confirmed that the blood vessel model was not sufficiently gelled,had scarcely resilience, and also had fluidity and stickiness on itssurface. Therefore, this model was unsuitable for a blood vessel model.

Therefore, it can be seen that a blood vessel model cannot be obtained,since gelling of the obtained polyvinyl alcohol does not sufficientlyproceed, even though polyvinyl alcohol having an average polymerizationdegree of 1700 and a saponification degree of 99.0% by mole is mixedwith polyvinyl alcohol having an average polymerization degree of 1800and a saponification degree of 86 to 90% by mole in a weight ratio of80/20, and the mixture is dissolved in a mixed solvent of water anddimethyl sulfoxide and cooled to room temperature.

Comparative Example 3

The same procedures as in Comparative Example 1 were carried out exceptthat the polyvinyl alcohol solution was poured into the straight tubemade of an acrylic resin having a volume of 200 mL, that the temperaturefor cooling this resin container was changed from room temperature to−20° C., followed by freezing at this temperature for 24 hours, and thatthe temperature was returned to room temperature to thaw. As a result, agel was obtained unlike Comparative Example 1. However, it was confirmedthat the obtained gel had poor resilience and stickiness on its surface.

Comparative Example 4

A blood vessel model was produced by cutting a commercially availablesilicone rubber tube having a diameter of 2 mm into pieces each having alength of 20 cm.

Test Example 1

As physical properties, appearance, water wettability (hydrophilicity),sticky feeling, resilience and incision feeling of blood vessel modelsobtained in each Example and each Comparative Example were examined inaccordance with the following methods. The results are shown in Table 1.

(1) Appearance

Ten students and teachers who majored in surgery in a graduate school ofmedicine of a university were asked to observe the appearance of eachblood vessel model, and the appearance was evaluated in accordance withthe following evaluation criteria. Incidentally, acceptable standard isthat nobody rates “D”.

[Evaluation Criteria]

A: hardly distinguishable from a blood vessel of living bodyB: very similar to a blood vessel of living bodyC: sufficiently similar to a blood vessel of living bodyD: unsimilar to a blood vessel of living body

(2) Water Wettability (Hydrophilicity)

A water drop was dropped on the blood vessel model, and ten students andteachers who majored in surgery in a graduate school of medicine of auniversity were asked to observe the surface of the blood vessel modelwith naked eyes. The water wettability was evaluated in accordance withthe following evaluation criteria. Incidentally, acceptable standard isthat nobody rates “D”.

[Evaluation Criteria]

A: hardly distinguishable from a blood vessel of living bodyB: very similar to a blood vessel of living bodyC: sufficiently similar to a blood vessel of living bodyD: unsimilar to a blood vessel of living body

(3) Sticky Feeling

Ten students and teachers who majored in surgery in a graduate school ofmedicine of a university were asked to examine sticky feeling of theblood vessel model by finger touching, and sticky feeling was evaluatedin accordance with the following evaluation criteria. Incidentally,acceptable standard is that nobody rates “D”.

[Evaluation Criteria]

A: hardly distinguishable from a blood vessel of living bodyB: very similar to a blood vessel of living bodyC: sufficiently similar to a blood vessel of living bodyD: unsimilar to a blood vessel of living body

(4) Resilience

Ten students and teachers who majored in surgery in a graduate school ofmedicine of a university were asked to examine resilience of the bloodvessel model by finger touching, and the resilience was evaluated inaccordance with the following evaluation criteria. Incidentally,acceptable standard is that nobody rates “D”.

[Evaluation Criteria]

A: hardly distinguishable from a blood vessel of living bodyB: very similar to a blood vessel of living bodyC: sufficiently similar to a blood vessel of living bodyD: unsimilar to a blood vessel of living body

(5) Incision Feeling

Ten students and teachers who majored in surgery in a graduate school ofmedicine of a university were asked to examine incision feeling of eachblood vessel model by actually operating with a surgical scalpel[surgical change-edge surgical knife No. 10 made of stainless steel,manufactured by FEATHER Safety Razor Co., Ltd.], and incision feelingwas evaluated in accordance with the following evaluation criteria.Incidentally, acceptable standard is that nobody rates “D”.

[Evaluation Criteria]

A: hardly distinguishable from a blood vessel of living bodyB: very similar to a blood vessel of living bodyC: sufficiently similar to blood vessel of living bodyD: unsimilar to blood a vessel of living body

In Comparative Example 1, since a gel could not be produced, physicalproperties of the blood vessel model could not be determined.

TABLE 1 Physical properties of blood vessel model Example and WaterSticky Incision Comparative Appearance wettability feeling Resiliencefeeling Example No. A B C D A B C D A B C D A B C D A B C D 1 9 1 0 0 91 0 0 8 2 0 0 9 1 0 0 9 1 0 0 2 7 2 1 0 9 1 0 0 7 2 1 0 8 2 0 0 9 1 0 03 7 1 2 0 9 1 0 0 7 3 0 0 8 1 1 0 8 1 1 0 4 7 2 1 0 8 2 0 0 8 2 0 0 8 20 0 8 2 0 0 5 8 1 1 0 8 2 0 0 7 2 1 0 7 3 0 0 7 2 1 0 Comp. Ex. 1 6 2 20 5 4 1 0 2 4 3 1 1 1 4 4 0 1 5 4 2 — — — — — — — — — — — — — — — — — —— — 3 7 3 0 0 5 3 1 1 0 0 2 8 0 0 3 7 0 0 4 6 4 7 3 0 0 0 0 1 9 2 3 3 21 2 3 4 0 0 2 8

It can be seen from the results shown in Table 1 that the blood vesselmodel obtained in each Example has appearance and water wettabilitysimilar to a blood vessel of the living body and a surface free fromstickiness, and also has resilience and incision feeling like a bloodvessel of the human body, since the blood vessel model containingpolyvinyl alcohol and silica particles is used.

Example 6

Two blood vessel models each having an outer diameter of 4 mm, an innerdiameter of 2 mm and a length of 200 mm were produced in the same manneras in Example 1. The two blood vessel models were intersected with eachother, and a hole having a diameter of about 2 mm was formed at theintersected portion in each blood vessel model. The two blood vesselmodels were connected with each other so that the inside of each bloodvessel model was communicated with each other, and the mixed solutionobtained in Example 1 was applied to the intersected portion so as toseal the intersected portion.

In the obtained blood vessel model integrated by intersecting the twoblood vessel models, an opening having a diameter of about 2 mm wasformed on the side surface of one of the blood vessel models.

Apart from this blood vessel model, a large aneurysm-shaped blood vesselmodel which imitated an aneurysm was produced by using the mixedsolution obtained in Example 1. More specifically, this aneurysm-shapedblood vessel model was produced by applying the mixed solution obtainedin Example 1 to the surface of a rubber balloon expanded by blowing airto have a diameter of about 8 mm; carrying out freezing and thawing inthe same manner as in Example 1 to produce an aneurysm-shaped bloodvessel model; pricking the blood vessel model with a needle therebycausing the balloon to rupture inside the blood vessel model; removingthe needle; and then taking out the balloon from the formed openinghaving a diameter of about 2 mm.

The opening of the aneurysm-shaped blood vessel model obtained in theabove was intersected with the opening positioned at the side surface ofthe blood vessel model produced by intersecting and integrating the twoblood vessel models obtained in the above, and the inside of each bloodvessel model was communicated with each other. The mixed solutionobtained in Example 1 was applied to the intersected portion so as toseal the intersected portion. Thereafter, freezing and thawing of themodel was carried out in the same manner as in Example 1, to give ablood vessel model having an aneurysm-shaped blood vessel. An acrylicposter color having a red color similar to the color of human blood[manufactured by Delta Corporation under the trade name ofDeltaCeramcoat] was filled into the obtained blood vessel model. Theobtained blood vessel model is shown in FIG. 3.

FIG. 3 is a photograph, which is substituted for a drawing, of the bloodvessel model obtained in the above. As shown in FIG. 3, it can be seenthat a liquid similar to blood (black area in the drawing) exists insidethe obtained blood vessel model, and that a lump similar to an aneurysmexists on the left side of the intersected portion of the two bloodvessel models in the blood vessel model which extends in a lateraldirection facing the drawing.

Next, the surgeon was asked to observe the obtained blood vessel model.As a result, as to this blood vessel model, there could be obtained highevaluation, such that the blood vessel model could be sufficientlyexpected to be used as a blood vessel model for practicing surgery forimplanting an artificial blood vessel in an aneurysm, a blood vesselmodel for practicing insertion of a stent graft into an aneurysm, andthe like.

From the above facts, it can be seen that the blood vessel model of thepresent invention can be suitably used, for example, as a blood vesselmodel for practicing insertion of a stent graft into an aneurysm, ablood vessel model for practicing resection or ligation surgery of ablood vessel, and the like.

Example 7

A 500 mL volume beaker was charged with 80 mL of dimethyl sulfoxide and20 mL of water, and they were sufficiently mixed with each other, togive a mixed solvent. To 100 mL of the mixed solvent in the abovebeaker, 20 mL of colloidal silica [manufactured by Nissan ChemicalIndustries, Ltd. under the trade name of SNOWTEX XP, particle diameterof silica: about 5 nm, content of silica: 5% by weight] was added,followed by stirring so that the contents in the beaker became uniform.

Next, polyvinyl alcohol having an average polymerization degree of 1700and a saponification degree of 98 to 99% by mole or so [manufactured byKURARAY CO., LTD. under the trade name of KURARAY POVAL PVA-117] wasadded to the beaker to have a concentration of 10% by weight. Themixture was stirred for 15 minutes while heating to 80° C., to give amixed solution.

To the obtained mixed solution, 0.15 mL of a semitransparent acrylicposter color having a chestnut color similar to the color of a humanblood vessel [manufactured by Delta Corporation under the trade name ofDeltaCeramcoat] was added, followed by stirring, to form homogeneouscomponents.

A rubber plug made of a silicone rubber was inserted to the opening atone end of a straight tube made of an acrylic resin having an outerdiameter of 5 mm, an inner diameter of 4 mm and a length of 200 mm, anda core material made of an acrylic resin having a diameter of 2 mm and alength of 250 mm was inserted to the hole for inserting a core materialformed at the central portion of the rubber plug. The opening positionedat another end of this straight tube was facing upward, and the tintedmixed solution obtained in the above (liquid temperature: 45° C.) waspoured into the gap between the straight tube and the core material upto the vicinity of the opening at another end of the straight tube sothat no air bubbles infiltrated. Thereafter, a core material waspenetrated to the hole for inserting a core material formed at thecentral portion of the rubber plug made of a silicone rubber, and therubber plug was inserted to the opening of the straight tube.

Next, this straight tube was placed in a freezing chamber (temperaturein the freezing chamber: −20° C.), cooled for 6 hours, taken out fromthe freezing chamber and then allowed to stand at room temperature tohave room temperature.

The obtained blood vessel model was taken out from this straight tube,and the core material was taken out from this blood vessel model. Thisblood vessel model was dipped in water in a container charged with 5 Lof water at 25° C. The container was allowed to stand for 24 hours whilesupplying water to this container at a flow rate of 200 mL/min, and thenthe blood vessel model was taken out from the container.

An acrylic poster color having a red color similar to the color of humanblood [manufactured by Delta Corporation under the trade name ofDeltaCeramcoat] was filled into a part of the inner space of this bloodvessel model. The blood vessel model thus obtained is shown in FIG. 4.FIG. 4 is a photograph, which is substituted for a drawing, of the bloodvessel model obtained in the above. As shown in FIG. 4, it can be seenthat a liquid similar to blood (black area in the drawing) exists insidethe obtained blood vessel model, and that the blood vessel model has aform similar to a blood vessel of the human body.

Example 8

A blood vessel model was produced in the same manner as in Example 7,except that polyvinyl alcohol having an average polymerization degree of1000 and a saponification degree of about 98 to about 99% by mole[manufactured by KURARAY CO., LTD under the trade name of KURARAY POVALPVA-110] was used as polyvinyl alcohol in Example 7.

Example 9

A blood vessel model was produced in the same manner as in Example 7,except that polyvinyl alcohol having an average polymerization degree of2000 and a saponification degree of about 98 to about 99% by mole[manufactured by KURARAY CO., LTD. under the trade name of KURARAY POVALPVA-120] was used as polyvinyl alcohol in Example 7.

Example 10

A blood vessel model was produced in the same manner as in Example 7,except that the amount of colloidal silica was changed to 5 mL inExample 7.

Example 11

A blood vessel model was produced in the same manner as in Example 7,except that the amount of colloidal silica was changed to 50 mL inExample 7.

Example 12

A blood vessel model was produced in the same manner as in Example 7,except that 75 mL of dimethyl sulfoxide and 25 mL of water were used inplace of 80 mL of dimethyl sulfoxide and 20 mL of water in Example 7.

Example 13

A blood vessel model was produced in the same manner as in Example 7,except that 85 mL of dimethyl sulfoxide and 15 mL of water were used inplace of 80 mL of dimethyl sulfoxide and 20 mL of water in Example 7.

Comparative Example 5

A blood vessel model was produced in the same manner as in Example 7,except that the colloidal silica was not used in Example 7.

Comparative Example 6

A polyvinyl alcohol powder (average polymerization degree: 1700,saponification degree: 99.0% by mole) in an amount of 80 g was mixedwith a polyvinyl alcohol powder (average polymerization degree: 1800,saponification degree: 86 to 90% by mole) in an amount of 20 g to obtaina polyvinyl alcohol mixture. The obtained polyvinyl alcohol mixture wasdissolved in a mixed solvent of dimethyl sulfoxide and water [dimethylsulfoxide/water (weight ratio): 80/20] while heating to 120° C. toprepare a polyvinyl alcohol solution having a water content of 80% byweight.

The same procedures as in Example 7 were carried out except that thepolyvinyl alcohol solution obtained in the above was used in place ofthe mixed solution used in Example 7, and the polyvinyl alcohol solution(liquid temperature: 45° C.) was poured into the gap between thestraight tube and the core material up to the vicinity of an opening atanother end of the straight tube so that no air bubbles infiltrated.Then, a core material was penetrated to the hole for inserting a corematerial formed at the central portion of a rubber plug made of asilicone rubber, and the rubber plug was inserted to the opening of thestraight tube.

Next, this straight tube was placed in a freezing chamber (temperaturein the freezing chamber: −20° C.), cooled for 6 hours, taken out fromthe freezing chamber and then allowed to stand at room temperature tohave room temperature. The rubber plug at both ends of this straighttube was removed and the core material was taken out from the straighttube. This straight tube was dipped in 200 mL of ethanol for 2 hours atroom temperature, and dimethyl sulfoxide was substituted with ethanol toremove. The straight tube was dipped in water at 25° C., and thisstraight tube was taken out from the water. The obtained blood vesselmodel was taken out from the straight tube.

This blood vessel model was observed with naked eyes. As a result, itwas confirmed that the blood vessel model was not sufficiently gelledand had scarcely resilience, and also had fluidity and stickiness on itssurface. Therefore, this model could not be used as a blood vesselmodel.

Accordingly, it can be seen that a blood vessel model cannot beobtained, since gelling of the obtained polyvinyl alcohol does notsufficiently proceed, even though polyvinyl alcohol having an averagepolymerization degree of 1700 and a saponification degree of 99.0% bymole is mixed with polyvinyl alcohol having an average polymerizationdegree of 1800 and a saponification degree of 86 to 90% by mole in aweight ratio of 80/20, and the mixture is dissolved in a mixed solventof water and dimethyl sulfoxide and cooled to room temperature.

Comparative Example 7

The same procedures as in Comparative Example 5 were carried out, exceptthat a polyvinyl alcohol solution was poured into a straight tube madeof an acrylic resin having a volume of 200 mL, and then the temperaturefor cooling this resin container was changed from room temperature to−20° C., that freezing was carried out at this temperature for 24 hours,and that the temperature was returning to room temperature to thaw. As aresult, a gel-like blood vessel model was obtained, unlike ComparativeExample 5. However, it was confirmed that the obtained blood vesselmodel has poor flexibility (resilience), and has stickiness on itssurface.

Test Example 2

As physical properties, transparency, water wettability(hydrophilicity), flexibility (resilience), sticky feeling and tensilestrength of the blood vessel models obtained in each Example and eachComparative Example were examined in accordance with the followingmethods. The results are shown in Table 2.

(1) Transparency

Each blood vessel model was observed with naked eyes, and transparencywas evaluated in accordance with the following evaluation criteria.

[Evaluation Criteria]

A: excellent transparencyB: satisfactory transparencyC: slightly poor transparencyD: poor transparency

(2) Water Wettability (Hydrophilicity)

A water drop was dropped on each blood vessel model, and the surface ofthe blood vessel model was observed with naked eyes. The waterwettability was evaluated in accordance with the following evaluationcriteria.

[Evaluation Criteria]

A: water wettability suitable for a blood vessel model for surgicaltrainingB: water wettability slightly suitable for a blood vessel model forsurgical trainingC: water wettability less suitable for a blood vessel model for surgicaltrainingD: unsuitable for a blood vessel model for surgical training

(3) Flexibility (Resilience)

Flexibility (resilience) of each blood vessel model was examined byfinger touching, and evaluated in accordance with the followingevaluation criteria.

[Evaluation Criteria]

A: flexibility (resilience) suitable for a blood vessel model forsurgical trainingB: flexibility (resilience) slightly suitable for a blood vessel modelfor surgical trainingC: flexibility (resilience) less suitable for a blood vessel model forsurgical trainingD: unsuitable for a blood vessel model for surgical training

(4) Sticky Feeling

Sticky feeling of each blood vessel model was examined by fingertouching, and evaluated in accordance with the following evaluationcriteria.

[Evaluation Criteria]

A: scarcely stickyB: a little sticky but no hindranceC: clearly stickyD: considerably sticky

(5) Tensile Strength

Both ends of each blood vessel model were pinched with a thumb and thefirst finger of both hands, and then drawn. The tensile strength wasevaluated in accordance with the following evaluation criteria.

[Evaluation Criteria]

A: excellent tensile strengthB: satisfactory tensile strengthC: slightly poor tensile strengthD: poor tensile strength

In Comparative Example 6, since a gel could not be produced, physicalproperties of the blood vessel model could not be examined.

TABLE 2 Ex. and Physical properties of blood vessel model Comp. Ex.Water Sticky Tensile No. Transparency wettability Flexibility feelingstrength 7 A A A A A 8 A A A A B 9 A B B A A 10  B B A B A 11  A B A A A12  A A A A A 13  B B B B B Comp. Ex. 5 B B C C D 6 — — — — — 7 C C D DD

From the results shown in Table 2, it can be seen that the blood vesselmodel obtained in each Example is excellent in transparency and hasmoderate hydrophilicity and flexibility, and has a surface free fromstickiness and large tensile strength.

Example 14

Two blood vessel models each having an outer diameter of 4 mm, an innerdiameter of 2 mm and a length of 200 mm were produced in the same manneras in Example 7. The two blood vessel models were intersected with eachother, and a hole having a diameter of about 2 mm was formed at theintersected portion in each blood vessel model. The two blood vesselmodels were connected with each other so that the inside of each bloodvessel model was communicated with each other, and the mixed solutionobtained in Example 7 was applied to the intersected portion so as toseal the intersected portion.

In the obtained blood vessel model integrated by intersecting the twoblood vessel models, an opening having a diameter of about 2 mm wasformed on the side surface of one of the blood vessel models.

Apart from this blood vessel model, a large aneurysm-shaped blood vesselmodel which imitated an aneurysm was produced by using the mixedsolution obtained in Example 7. More specifically, this aneurysm-shapedblood vessel model was produced by applying the mixed solution obtainedin Example 7 to the surface of a rubber balloon expanded by blowing airto have a diameter of about 8 mm; carrying out freezing and thawing inthe same manner as in Example 7 to produce an aneurysm-shaped bloodvessel model; pricking the blood vessel model with a needle, and therebycausing the balloon to rupture inside the blood vessel model; removingthe needle; and then taking out the balloon from the formed openinghaving a diameter of about 2 mm.

The opening of the aneurysm-shaped blood vessel model obtained in theabove was intersected with the opening positioned at the side surface ofthe blood vessel model produced by intersecting and integrating twoblood vessel models obtained in the above, and the inside of each bloodvessel model was communicated with each other. The mixed solutionobtained in Example 7 was applied to the intersected portion so as toseal the intersected portion. Thereafter, freezing and thawing of themodel was carried out in the same manner as in Example 7, to give ablood vessel model having an aneurysm-shaped blood vessel. An acrylicposter color having a red color similar to the color of human blood[manufactured by Delta Corporation under the trade name ofDeltaCeramcoat] was filled into the obtained blood vessel model. Theobtained blood vessel model is shown in FIG. 5.

FIG. 5 is a photograph, which is substituted for a drawing, of the bloodvessel model obtained in the above. As shown in FIG. 5, it can be seenthat a liquid similar to blood (black area in the drawing) exists insidethe obtained blood vessel model, and that a lump similar to an aneurysmexists on the left side of the intersected portion of the two bloodvessel models in the blood vessel model which extends in a lateraldirection facing the drawing.

From the above facts, it can be seen that the blood vessel model of thepresent invention can be suitably used, for example, as a blood vesselmodel for practicing insertion of a stent graft into an aneurysm, ablood vessel model for practicing resection or ligation surgery of ablood vessel, and the like.

REFERENCE SIGNS LIST

-   -   1: Aorta    -   2: Large aneurysm    -   3 Stent graft    -   4: Catheter

1. A method for producing a blood vessel model which imitates a humanblood vessel, comprising filling a mixed solution containing polyvinylalcohol having an average polymerization degree of 300 to 3500 and asaponification degree of 90% by mole or more, silica particles and waterin a mold for forming a blood vessel model, and freezing the mixture ata temperature of −10° C. or lower, and thereafter thawing the mixture.2. The method for producing a blood vessel model according to claim 1,wherein colloidal silica is used as the silica particles.
 3. The methodfor producing a blood vessel model according to claim 1, wherein theamount of the silica particles is from 0.01 to 50 parts by weight basedon 100 parts by weight of the polyvinyl alcohol.
 4. The method forproducing a blood vessel model according to claim 1, wherein theconcentration of the polyvinyl alcohol in the mixed solution is from 1to 40% by weight.
 5. The method for producing a blood vessel modelaccording to claim 1, wherein the temperature of the blood vessel modelformed after thawing is controlled to 35° to 80° C.
 6. The method forproducing a blood vessel model according to claim 1, wherein the mixedsolution further comprises dimethyl sulfoxide.
 7. The method forproducing a blood vessel model according to claim 6, wherein the ratioof the dimethyl sulfoxide to water (dimethyl sulfoxide/water: volumeratio) is from 50/50 to 95/5.